The long-range objective of the proposed research is to identify and analyze in sequential fashion, the key pathological changes occurring during oral carcinogenesis. Full thickness whole mounts and viable single cell dissociates of carcinogen treated hamster buccal pouch epithelium (HBPE) will be examined for histochemical, morphological and functional evidence of cells which have undergone one or more steps in the carcinogenic process. Emphasis will be placed on the role of carcinogen induced HBPE cells with histochemical activity for gamma-glutamyl transpeptidase (GGT), a marker for presumptive initiation sites in this model. The specific aims are: 1) to characterize the GGT+ sites with regard to their (a) origin in individual replicating cells, (b) resistance to cytotoxicity, and (c) persistence; 2) to evaluate the potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin to serve as a promoting agent for HBPE; 3) to enzymatically dissociate initiated HBPE and determine whether the isolated cells manifest (a) an enhanced capacity for survival and growth in vitro, (b) altered differentiation in vitro, and (c) angiogenic and tumorigenic potential. This research is based on the premise that improved strategies for the early detection or prevention of oral cancer will require a thorough familiarity with the phenotypic properties of precancerous oral lesions and a detailed knowledge of the mechanisms involved in their induction and subsequent evolution to cancer.